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Endocrine
Published in: Endocrine 2/2018

01-02-2018 | Original Article

Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors

Authors: Aura D. Herrera-Martínez, Manuel D. Gahete, Sergio Pedraza-Arevalo, Rafael Sánchez-Sánchez, Rosa Ortega-Salas, Raquel Serrano-Blanch, Raúl M. Luque, María A. Gálvez-Moreno, Justo P. Castaño

Published in: Endocrine | Issue 2/2018

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Abstract

Purpose

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1–sst5) in GEP-NETs.

Methods

The expression of SST system components in GEP-NETs was determined, compared with that of non-tumor adjacent and normal tissues and correlated with clinical and histological characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples were included. Cell viability in NET cell lines was determined in response to specific SSAs.

Results

Normal samples and non-tumor adjacent tissues presented a similar expression profile, with appreciable expression of sst2 and sst3, and a lower expression of the other receptors. In contrast, cortistatin, sst1, sst4, and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed in less differentiated tumors. Some SST system components were related to vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced viability in BON-1 cells, while they, similar to octreotide and pasireotide, increased viability in QGP-1 cells.

Conclusions

These results provide novel information on SST system pathophysiology in GEP-NETs, including relevant associations with clinical-histological parameters, which might help to better understand the intrinsic heterogeneity of NETs and to identify novel biomarkers and/or targets with potential prognostic and/or therapeutic value for GEP-NETs patients.
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Metadata
Title
Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors
Authors
Aura D. Herrera-Martínez
Manuel D. Gahete
Sergio Pedraza-Arevalo
Rafael Sánchez-Sánchez
Rosa Ortega-Salas
Raquel Serrano-Blanch
Raúl M. Luque
María A. Gálvez-Moreno
Justo P. Castaño
Publication date
01-02-2018
Publisher
Springer US
Published in
Endocrine / Issue 2/2018
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-017-1482-3

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